Brain-Behavioral Predictors of Interpersonal Stress Generation and Depression Risk in Adolescent Girls

严重抑郁障碍(MDD)发病的风险在青春期显著增加，特别是对女孩。 迫切需要阐明MDD风险的潜在机制，以改进早期风险检测和 有针对性的预防。压力生成模型假设人际压力生成(I-StressGen)是一种 风险机制，并建议具有先前存在的MDD脆弱性的青年积极为 在他们的生活中发生人际关系紧张的生活事件(即I-StressGen)，这反过来会加剧他们的 MDD的风险。尽管I-StressGen对青少年潜在MDD风险的影响是众所周知的， 导致i-StressGen的确切机制尚不清楚。自我报告研究表明增加了 负面社会互动中的情感反应是促进I-StressGen的一种有前途的机制， 尽管这还没有经过直接的测试。I-StressGen的潜在神经机制也仍然存在 未经研究，尽管研究表明，更大的社会压力与大脑中的异常激活有关 在任务探测过程中，大脑皮质边缘区域对消极的社会互动做出反应。因此，最重要的是 这项拟议的研究的目标是对大脑和大脑的作用有一个精细的、机械性的理解 负性社交中的行为情感反应与I-StressGen及后续的关系 女性青少年中的MDD风险。这项拟议的研究将招募90名女性青少年的风险增强样本 (13-15岁)，并将利用神经成像(FMRI)和生态瞬时评估(EMA)来检查大脑 和社会情感反应的行为指数作为I-StressGen和抑郁症状的预测因子 多波一年的随访。在这样做的过程中，目前的研究将测试消极情绪下的情感反应是否 神经(目标1)和真实世界行为(目标2)层面的社会互动前瞻性地预测I- StressGen，以及I-StressGen是否在这种社会情感反应和 女青少年抑郁症状的预期增加(目标3)。拟议的研究和平行 培训计划将使候选人能够利用她目前在青少年压力和MDD风险方面的专业知识，并 开发四个关键领域的新技能：(1)功能磁共振成像，(2)EMA，(3)高级统计多水平建模，和(4) 职业发展。伊利诺伊大学芝加哥分校丰富的学术环境与 候选人的指导团队在功能磁共振成像方法学、发展情感 神经科学、EMA和先进的统计技术将促进拟议的 学习和培训计划。获得这些技能将是启动候选人的独立 翻译科学家的职业生涯，专注于描绘青少年MDD风险的脑行为机制 在现实世界人际压力的背景下。这项研究的结果将为未来的发展提供参考 基金侧重于表征社会情感大脑和行为机制以及异常发育 青春期出现适应不良应激过程和MDD发病的轨迹。

Risk for major depressive disorder (MDD) onset dramatically increases during adolescence, particularly for girls. There is a vital need to elucidate the underlying mechanisms of MDD risk to improve early risk detection and targeted preventions. The stress generation model posits interpersonal stress generation (I-StressGen) as a mechanism of risk and proposes that youth with preexisting MDD vulnerabilities actively contribute to the occurrence of interpersonal stressful life events in their lives (i.e., I-StressGen), which in turn exacerbates their risk for MDD. Although the impact of I-StressGen on prospective MDD risk in adolescents is well-established, the precise mechanisms contributing to I-StressGen remain unclear. Self-report research indicates increased affective reactivity during negative social interactions as a promising mechanism contributing to I-StressGen, though this has not been directly tested. The underlying neural mechanisms of I-StressGen also remain unexamined, despite work suggesting that greater social stress is associated with aberrant activation in corticolimbic regions during tasks probing response to negative social interactions. Therefore, the overarching goal of the proposed study is to obtain a fine-grained, mechanistic understanding of the role of brain and behavioral affective reactivity during negative social interactions as it relates to I-StressGen and subsequent MDD risk in female adolescents. The proposed study will enroll a risk-enhanced sample of 90 female adolescents (ages 13-15) and will utilize neuroimaging (fMRI) and ecological momentary assessment (EMA) to examine brain and behavior indices of socio-affective reactivity as predictors of I-StressGen and depression symptoms across a multi-wave one year follow-up. In doing so, the current study will test whether affective reactivity during negative social interactions at the neural (Aim 1) and real-world behavioral (Aim 2) level prospectively predicts I- StressGen, and whether I-StressGen mediates the relation between this socio-affective reactivity and prospective increases in female adolescents’ depression symptoms (Aim 3). The proposed study and parallel training plan will allow the Candidate to build upon her current expertise in adolescent stress and MDD risk and develop new skills in four key areas: (1) fMRI, (2) EMA, (3) advanced statistical multilevel modeling, and (4) professional development. The rich academic environment at the University of Illinois at Chicago coupled with the collective expertise of the Candidate’s mentorship team in fMRI methodology, developmental affective neuroscience, EMA, and advanced statistical techniques will facilitate successful implementation of the proposed study and training plan. The acquisition of these skills will be integral to launching the Candidate’s independent career as a translational scientist focused on delineating brain-behavioral mechanisms of adolescent MDD risk within the context of real-world interpersonal stress. Results from this study will inform the development of future grants focused on characterizing socio-affective brain and behavior mechanisms and aberrant developmental trajectories contributing to the emergence of maladaptive stress processes and MDD onset in adolescence.